As assessed with microdialysis procedures, a cocaine challenge administered systemically produced a higher elevation of extracellular dopamine (DA) in either the n. accumbens or striatum following chronic administration of cocaine for seven days. On the other hand, when rats were challenged with cocaine through microdialysis probes in either the n. accumbens or striatum, there was no difference in DA overflow between saline and cocaine pretreated rats. Apomorphine injected into the substantia nigra or VTA produced a dose-dependent decrease in extracellular DA in the striatum and n. accumbens, respectively. No difference was seen in apomorphine-induced inhibition of extracellular DA between rate that had been treated chronically with saline or cocaine. The enhancement in DA overflow induced by a systemic cocaine challenge in chronic cocaine-pretreated rats cannot be due to alterations in presynaptic DA function or to alterations in DA auto receptor sensitivity. Autoradiographic studies revealed that chronic cocaine does not alter D1 or D2 DA receptors, the DA uptake site or tyrosine hydroxylase.